The goals of the current Specialized Center for Cell-Based Therapy (SCCT) application are to implement highly feasible clinical studies that provide significant improvements on already tested approaches. The two clinical proposals use a newly developed suicide gene system (Project 1) and pathogen specific T cells (Project 2) as means of improving the safety and effectiveness of cellular therapeutics. These studies are combined with a preclinical Project 3 that exploits models of cardiac disease to identify methods that can subsequently be tested in the clinic with our cardiologist colleagues who already have exploratory cell therapy trials for cardiac disease. These projects are supported by four cores that will provide support in A) Administration, B) Clinical and Regulatory affairs and Biostatistics, C) GMP manufacturing of cells and vectors for clinical trials, and D) Flow Cytometry. These three projects and cores are mutually supportive and should interact synergistically to promote the general theme of this application, that many of the limitations of cellular therapy can be overcome by testing potential solutions in carefully designed specific clinical and preclinical settings. Our group has a decade-long history of successful and timely implementation of clinical translational projects in cellular therapy, and we have the resources to supply and test ail the clinical reagents required since the Center in which these studies will be performed is a National Gene Vector laboratory and one of three national Production Assistance for Cellular Therapy centers selected by NHLBI. We will thus have the background and resources to address three major concerns in cellular therapy: a) How can cellular therapies be safely controlled after they have been administered (Projects 1, 2 and 3)? b) How can patients be given sufficient immunosuppression to accept allogeneic cellular grafts without succumbing to lethal infections (Projects 1 and 2)? c) How can we identify the appropriate precursor cells for therapeutic use and ensure their optimal incorporation into existing host tissue (Projects 2 and 3)? Our expertise in adoptive therapy with T cells (Malcolm Brenner, Cliona Rooney, and Helen Heslop) and with hematopoietic and cardiac stem cells (Margaret Goodell and Michael Schneider) will allow us to develop clinical and preclinical systems in which these questions can be addressed and resolved.